B R I T I S H J O U R N A L O F P S YC H I AT RY ( 2 0 0 3 ) , 1 8 3 , 2 8 2 ^ 2 8 4
Understanding the suicidal brain
fl ICfl
C. VAN HEERINGEN and A. MARUS
MARUSIC
It has been suggested that the key to
preventing suicide is not in the study of
the brain, but in the direct study of the
human emotions (Shneidman, 1996).
However, recent advances in neuroscience
are providing support for a theory of
human emotions that implicates increas-
ingly well-defined brain regions (Stuss
et al,
al, 2001). The frontal lobes appear to
be essential, with the right frontal lobe
having a central role in the neural network
for social cognition, including inferences
about feelings of others. The ventral medial
frontal regions are also important, possibly
through their connections with the amyg-
dala and other limbic structures which
give them a key role in the neural network
for behavioural modulation based upon
emotion and drives (Phillips, 2003). It has
been difficult to dissociate social cognitive
processes from the behavioural expression
of these processes, but insights are rapidly
increasing based upon recent neuropsycho-
logical and neuroimaging studies.
Brain regions shown to be involved in
suicidal behaviour constitute what may be
called the ‘suicidal brain’. Moreover, the
current state of knowledge of neuropsycho-
logical and cognitive psychological aspects
of suicidal behaviour allows for a descrip-
tion of the roles of these areas in the
development of suicidal ideation and
behaviour, and more particularly for a dis-
sociation of the social cognitive processes
and the behavioural expression of these
processes. It is now clear that these brain
structures contribute to the trait-like char-
acteristics that constitute the vulnerability
to suicidal behaviour.
SUICIDE RISK: FROM BODY
TO BR AIN
One can show that there is an association
between brain dysfunction and suicidal
behaviour by comparing the risk of suicide
behaviour in various groups of physical
282
disorders. The risk of suicide increases the
nearer the disorder or dysfunction is to
the brain. When compared with the general
population, suicide risk is doubled in
people with disorders such as diabetes and
cancer, approximately five times greater in
people with peripheral neurological dis-
orders (e.g. 2–7 times greater in multiple
sclerosis and 4–9 times greater in spinal
cord lesions) and more than five times
greater in people with central neurological
disorders such as stroke and epilepsy (parti-
cularly treatment-resistant epilepsy: 25
times) (Stenager & Stenager, 2000).
The prevalence of mental disorders,
being strongly associated with an increased
risk of suicidal behaviour, also increases as
the primary location of the disorder or
dysfunction moves closer to the brain.
However, this probably does not explain
sufficiently the association between brain
dysfunction and the occurrence of suicidal
behaviour. Indeed, certain personality traits
that are also involved in the development of
suicidal behaviour (e.g. emotional lability,
impulsivity and aggressivity) are found in
ascending order of frequency in the general
population, those who are physically ill
(e.g. hostility in coronary disease) and those
with brain disorders (e.g. personality
changes in epilepsy or brain injury).
COGNITION AND THE
SUICIDAL BR AIN
Knowledge about the state of mind of
suicidal individuals remains limited.
Although thoughts and attitudes around
the time of a suicidal act may predict future
suicidal behaviour (Beck et al,
al, 1999), rela-
tively little is known about the most basic
aspects of cognitive processing in suicidal
individuals. However, impaired cognitive
functioning in psychiatric disorders for
which suicide risk is elevated is now well
documented (Mann et al, al, 1999), and in-
sight into the cognitive characteristics of
E D I TOR I A L
suicidal individuals is increasing (Williams
& Pollock, 2001). It has thus become clear
that three characteristics differentiate peo-
ple with depression who are suicidal from
people with depression who are not. These
characteristics include:
(a) a sensitivity to particular life events
reflecting signals of defeat, based on
attentional biases (‘perceptual pop-
out’) leading to involuntary hypersensi-
tivity to stimuli signalling ‘loser’ status;
(b) the sense of being trapped, which is
related to an insufficient capacity to
solve problems, commonly of an inter-
personal or social nature;
(c) the absence of rescue factors, mediated
by deficient prospective cognitive
processes and leading to feelings of
hopelessness.
Although the involvement of these
cognitive characteristics in the development
of suicidal behaviour has been shown con-
sistently, little is known about their neural
basis.
With regard to sensitivity to life events,
early studies focused on the hypothesis that
a generalised cognitive rigidity mediates the
relationship between stressful life events
and suicidal behaviour. However, more
recent findings are consistent with the poss-
ibility that among people with depression
those who attempt suicide differ from those
who do not on some but not all neuro-
psychological tests (King et al,
al, 2000). Using
a modified Stroop task, Becker et al (1999)
found that the level of suicidal ideation in
people with depression correlated parti-
cularly with biases in selective attention.
Another study could not demonstrate any
difference in attention measures between
suicide attempters and non-attempters in a
group of people with depression (Keilp
et al,
al, 2001). Although clearly much more
research is needed, these findings suggest a
role of attentional bias in the development
of suicidal ideation – but not suicidal
behaviour – in people with depression.
Williams & Pollock (2001) have con-
vincingly argued with regard to the second
characteristic that the sense of being
trapped is associated with trait-dependent
deficiencies in problem-solving skills,
which in turn appear to depend upon defi-
cits in autobiographical memory. Several
studies have shown an association between
attempted suicide and overgeneral autobio-
graphical memory (Evans et al, al, 1992;
Sidley et al,
al, 1997). These studies indicate
that overgeneral autobiographical recall

(probably mediated by the frontal lobes)
affects suicidal behaviour by its effect on
the ability to recall specific memories
among people who attempt suicide, which
correlates positively with the effectiveness
of the solutions suggested for solving
hypothetical social problems.
With regard to the third cognitive char-
acteristic, the relatively new research
approach addressing prospective cognition
may well be useful. One study (Audenaert
et al,
al, 2002) but not another (McLeod et
al,
al, 1993) found differences between those
who had attempted suicide and a non-
depressed control group using a neutral
fluency task. By using a modified fluency
test it was recently demonstrated that parti-
cipants who had attempted suicide were
less fluent in coming up with positive events
that might happen in the future. Moreover,
hopelessness – which is a core psycho-
pathological characteristic in association
with suicidal behaviour – was found to
correlate significantly with the lack of gen-
erating future positive events and not with
an excessive anticipation of negative things
in the future (Williams & Pollock, 2001).
Using a split-dose activation paradigm with
the Verbal Fluency Test we recently showed
a blunted increase in prefrontal blood flow
in the brains of people who had attempted
suicide when compared with a healthy
control group (Audenaert et al,al, 2002).
It thus appears that these three core
cognitive psychological characteristics are
associated with biases in neuropsychologi-
cal functioning in terms of attention,
memory and fluency, respectively.
Neural substrate of suicidal
cognitive processes
Recent neurobiological findings converge
to a substantial level with this cognitive
and neuropsychological approach, leading
to insights into the dissociation of social
cognitive processes from behavioural
expression involved in suicidal behaviour
(Deakin, 1996; Van Heeringen, 2001).
The social cognitive component is thought
to be modulated by the frontal and tem-
poral cortices in conjunction with the
hippocampus, and mediated by the sero-
tonin (5-HT)1A and noradrenalin neuro-
transmission systems. Sensitivity to social
stimuli (measured by means of the person-
ality dimension reward dependence, suppo-
sedly mediated by the noradrenergic
system) strongly correlates with the activ-
ation of the stress system in those who
attempt suicide by violent means (Van
Heeringen et al,al, 2000). A second com-
ponent addresses executive functions,
which may be modulated by the prefrontal
cortex in conjunction with the amygdala
and mediated by 5-HT2A and dopamine,
and comprise, among others, the abilities
needed to achieve and maintain a
problem-solving set – the second of the
cognitive processes involved in suicidal
behaviour described above.
Suicidal behaviour occurs at the cross-
roads of the past (recent with regard to pre-
cipitating stressors, and more distant with
regard to its effect on our resilience against
these stressors) and the future (or at least
the way it is perceived on the basis of
previous experiences). The frontal lobes
are responsible for the integration of
sensations, perceptions, consciousness and
memory into organised and planned behav-
iours (Fuster, 1997), and the prefrontal
cortex thus also mediates prospective
cognitive processes. In vivo functional
neuroimaging recently demonstrated that
suicidal behaviour is associated with a
decreased binding potential of prefrontal
5-HT2A receptors, which in turn correlates
significantly with increased levels of hope-
lessness and of behavioural inhibition (Van
Heeringen et al,
al, 2003). In a similar way it
appears that dysfunctional attitudes, i.e.
negatively biased views of oneself, the world
and the future, are associated with cortical
5-HT2 binding (Meyer et al, al, 2003). It thus
appears that the third cognitive process
involved in suicidal behaviour, as described
above, is associated with a decreased seroto-
nergic functioning in the prefrontal cortex,
which may become manifest as increased
levels of hopelessness and behavioural
inhibition following exposure to adverse
circumstances. Based on these findings it
can be hypothesised that increased behav-
ioural inhibition (i.e. anxiety-based avoid-
ance) is the primary mechanism involved,
which might lead to suicidal behaviour only
in the presence of a (dopamine-driven?)
force, which is strong enough to break
through this inhibition and which might
manifest itself as hostility or aggression.
This may explain the association between
serotonergic dysfunction and impulsivity
or dysregulation of aggression, as found in
post-mortem studies of those who have died
by suicide (Mann et al,
al, 1999). Although this
has been recently questioned, particularly
with regard to the 5-HT2A system (De Deur-
waerdère
waerdere & Spampinato, 1999), serotonin
acts in an antagonistic way to dopamine,
T H E S U I C I D A L B R A IN
so that a depletion of serotonin might indeed
disinhibit aggressive behaviour.
There is thus increasing evidence that
the suicidal brain comprises different (con-
nected) cortical and subcortical brain struc-
tures, which constitute the social cognitive
and behavioural expressive components of
the predisposition for suicidal behaviour.
Insight into the neuropsychological basis
and neurobiological modulation of these
components is increasing. Evidence can be
found for a role of social cognitive pro-
cesses (a sensitivity to particular social
circumstances) and the behavioural expres-
sion of these processes (due to a dysregula-
tion of anxiety and/or aggression). The
dissection of the predisposition for suicidal
behaviour in the components as described
above is supported by studies of the neuro-
biological modulation of neuropsychologi-
cal functions. For instance, attention level
is related to noradrenalin release (Kodama
et al,
al, 2002), and drugs that influence
5-HT1A function (such as buspirone) select-
ively affect performance on neuropsycholo-
gical tests of memory and learning without
affecting executive functions; the reverse
appears to be the case for drugs that influ-
ence the 5-HT2 system (Deakin, 1996).
Animal studies have shown that a balance
between (hippocampal) 5-HT1A and
(cortical) 5-HT2 functioning is essential
for an adequate response to social stress
(McKittrick et al,
al, 1995). Further research
is needed to study the relevance of such
findings to the understanding of the suicidal
brain. Moreover, the effects of state-
dependent conditions (such as those asso-
ciated with the increased stress response
or with excessive alcohol intake) on sero-
tonergic neural activity requires further
study, because of their potential influence
on the course of the suicidal process (Van
Heeringen, 2001).
Although the proposed model of the pre-
disposition to suicidal behaviour most prob-
ably is to be regarded as simplistic, the
complexity of the cortico-subcortical circuits
involved in the different components of the
predisposition to suicidal behaviour, their
neuropsychological expression and their
neurobiological modulation may well reflect
the complexity of predicting and treating
suicidal ideation and behaviour.
DECLAR ATION OF INTEREST
None.
283
 I N G E N & M A RU Sfl I Cfl
VA N H E E R IN

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